| Title: |
GenomegaMap: within-species genome-wide d_N/d_S estimation from over 10,000 genomes |
| Authors: |
Wilson, D; Crook, DW; Peto, TEA; Walker, AS; Hoosdally, SJ; Gibertoni Cruz, AL; Carter, J; Grazian, Clara; Earle, SG; Kouchaki, S; Lachapelle, A; Yang, Y; Clifton, DA; Fowler, PW; Iqbal, Z; Hunt, M; Knaggs, J; Smith, EG; Rathod, P; Jarrett, L; Matias, D; Cirillo, DM; Borroni, E; Battaglia, S; Ghodousi, A; Spitaleri, A; Cabibbe, A; Tahseen, S; Nilgiriwala, K; Shah, S; Rodrigues, C; Kambli, P; Surve, U; Khot, R; NIemann, S; Kohl, TA; Merker, M; Hoffman, H; Todt, K; Plesnik, S; Ismail, N; Omar, SV; Joseph, L; Thwaites, G; Thoung, TNT; Ngoc, NH; Srinivasan, V; Walker, TM; Moore, D; Coronel, J; Solano, W; Gao, GF; He, G; Zhao, Y; Liu, C; Ma, A; Zhu, B; Laurenson, I; Claxton, P; Koch, A; Wilkinson, R; Lalvani, A; Posey, J; Gardy, J; Werngren, J; Paton, N; Jou, R; Wu, MH; Lin, WH; Ferrazoli, L; Siqueira de Oliveira, R; Arandjelovic, I; Chaipresert, A; Comas, I; Roig, CJ; Drobniewski, FA; Farhat, MR; Gao, Q; Hee, ROT; Sintchenko, V |
| Contributors: |
Rosenberg, Michael |
| Source: |
urn:ISSN:0737-4038 ; urn:ISSN:1537-1719 ; Molecular Biology and Evolution, 37, 8, 2450-2460 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2020 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
31 Biological Sciences; 3102 Bioinformatics and Computational Biology; 3105 Genetics; Biotechnology; Tuberculosis; Infectious Diseases; Genetics; Rare Diseases; Human Genome; Antimicrobial Resistance; Emerging Infectious Diseases; Infection; 3 Good Health and Well Being; DEAD-box RNA Helicases; Genetic Techniques; Genome; Bacterial; Models; Genetic; Mycobacterium tuberculosis; Selection; Silent Mutation; adaptation; big data; dN/dS; natural selection; parent-dependent mutation; recombination; CRyPTIC Consortium; anzsrc-for: 31 Biological Sciences |
| Description: |
The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters such as dN/dS, but analysing very large datasets poses a major statistical challenge. Here I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: (i) it is fast no matter how large the sample size and (ii) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well-estimated even when genomegaMap’s simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in M. tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/unsworks_66543; https://doi.org/10.1093/molbev/msaa069 |
| DOI: |
10.1093/molbev/msaa069 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_66543; https://unsworks.unsw.edu.au/bitstreams/f6c530a5-bb92-4304-9acd-33e49e306473/download; https://doi.org/10.1093/molbev/msaa069 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.970D9335 |
| Database: |
BASE |